Background: The benefit of levothyroxine treatment of subclinical hypothyroidism (SCH) is subject to debate. This study compared treatment satisfaction between older adults with SCH using... Show moreBackground: The benefit of levothyroxine treatment of subclinical hypothyroidism (SCH) is subject to debate. This study compared treatment satisfaction between older adults with SCH using levothyroxine or placebo. Methods: We analyzed pooled individual participant data from two randomized, double-blind, placebocontrolled trials investigating the effects of levothyroxine treatment in older adults with SCH. Communitydwelling participants aged ‡65 years, with SCH (persistent thyrotropin levels 4.60–19.99 mIU/L for >3 months and normal free T4 level), were included. Intervention dose titration until thyrotropin levels normalized, with a mock dose adjustment of placebo. Treatment satisfaction was determined during the final study visit using the Treatment Satisfaction Questionnaire for Medication (TSQM), encompassing perceived effectiveness, side effects, convenience, and global satisfaction, along with the participants’ desire to continue study medication after the trial. Results: We included 536 participants. At baseline, the median (interquartile range [IQR]) age was 74.9 (69.7– 81.4) years, and 292 (55%) were women. The median (IQR) thyrotropin levels were 5.80 (5.10–7.00) mIU/L at baseline in both groups; at final visit, 4.97 (3.90–6.35) mIU/L in the placebo and 3.24 (2.49–4.41) mIU/L in the levothyroxine group. After treatment, the groups did not differ significantly in global satisfaction (mean difference [CI] -1.1 [-4.5 to 2.1], p = 0.48), nor in any other domain of treatment satisfaction. These results held true regardless of baseline thyrotropin levels or symptom burden. No major differences were found in the numbers of participants who wished to continue medication after the trial (levothyroxine 35% vs. placebo 27%), did not wish to continue (levothyroxine 27% vs. placebo 30%), or did not know (levothyroxine 37% vs. placebo 42%) (p = 0.14). In a subpopulation with high symptom burden from hypothyroid symptoms at baseline, those using levothyroxine more often desired to continue the medication after the trial than those using placebo (mean difference [CI]: -21.1% [-35.6% to -6.5%]). Show less
Torp, N.; Israelsen, M.; Coenraad, M.; Papp, M.; Shawcross, D.; Korenjak, M.; ... ; MICROB PREDICT Consortium 2024
Introduction Human albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and... Show moreIntroduction Human albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and healthcare systems. A precision medicine approach with biomarkers to predict human albumin treatment response, so-called predictive biomarkers, could make this a viable treatment option in patients with cirrhosis and ascites.Methods and analysis ALB-TRIAL is a multinational, double-blind, placebo-controlled randomised controlled trial. We aim to validate a predictive biomarker, consisting of a panel of circulating metabolites, to predict the treatment response to human albumin in patients with cirrhosis and ascites. All enrolled patients are stratified into a high-expected or low-expected effect stratum of human albumin based on the biomarker outcome. After stratification, patients in each group are randomised into either active treatment (20% human albumin) or corresponding placebo (0.9% NaCl) every 10th day for 6 months. The primary outcome is the cumulative number of liver-related events (composite of decompensation episodes, transjugular intrahepatic shunt insertion, liver transplantation and death). Key secondary outcomes include time-to-event analysis of primary outcome components, an analysis of the total healthcare burden and a health economic analysis.Ethics and dissemination The trial obtained ethical and regulatory approval in Denmark, Germany, the Netherlands, Belgium, Hungary and Spain through the Clinical Trials Information System (CTIS) from 13 February 2023, while UK approvals from the Health Regulatory Authority, Medicines and Healthcare products Regulatory Agency and Research Ethics Committee are pending. Findings will be published in peer-reviewed journals, presented at conferences, communicated to relevant stakeholders and in the public registry of CTIS, following trial completion. Show less
BACKGROUND There are no data comparing sirolimus-coated balloons (SCBs [MagicTouch, Concept Medical]) to paclitaxel-coated balloons (PCBs [SeQuent Please Neo, B. Braun]) for the treatment of de... Show moreBACKGROUND There are no data comparing sirolimus-coated balloons (SCBs [MagicTouch, Concept Medical]) to paclitaxel-coated balloons (PCBs [SeQuent Please Neo, B. Braun]) for the treatment of de novo small vessel disease (SVD).OBJECTIVES This study sought to compare quantitative coronary angiographic outcomes at 6 months after treatment of de novo SVD with a PCB or SCB.METHODS This prospective, multicenter, noninferiority trial randomized 121 patients (129 SVD lesions) to treatment with an SCB or PCB, with balloon sizing determined using optical coherence tomography. The primary endpoint was noninferiority for the 6-month angiographic net lumen gain.RESULTS Angiographic follow-up was completed in 109 (90.1%) patients in the per-protocol analysis. The mean +/- SD angiographic net gains were 0.25 +/- 0.40 mm with SCBs vs 0.48 +/- 0.37 mm with PCBs, resulting in SCBs failing to meet the 0.30 mm criterion for noninferiority (P-noninferiority = 0.173), with an absolute difference of -0.23 mm (95% CI: -0.37 to -0.09) secondary to a smaller late loss (0.00 +/- 0.32 mm vs 0.32 +/- 0.47 mm; P < 0.001) and more frequent late lumen enlargement (53.7% vs 30.0%; OR: 2.60; 95% CI: 1.22-5.67; P = 0.014) with PCBs. Binary restenosis rates were 32.8% and 12.5% following treatment with SCBs and PCBs, respectively (OR: 3.41; 95% CI: 1.36-9.44; P = 0.012). The mean angiography-derived fractional flow ratio at follow-up was 0.86 +/- 0.15 following treatment with SCBs and 0.91 +/- 0.09 following PCBs (P = 0.026); a fractional flow ratio <= 0.80 occurred in 13 and 5 vessels after treatment with SCBs and PCBs, respectively.CONCLUSIONS The SCB MagicTouch failed to demonstrate noninferiority for angiographic net lumen gain at 6 months compared to the PCB SeQuent Please Neo. Show less
ObjectiveTo optimize treatment recommendations for eating disorders, it is important to investigate whether some individuals may benefit more (or less) from certain treatments. The current study... Show moreObjectiveTo optimize treatment recommendations for eating disorders, it is important to investigate whether some individuals may benefit more (or less) from certain treatments. The current study explored predictors and moderators of an automated online self-help intervention “Featback” and online support from a recovered expert patient.MethodsData were used from a randomized controlled trial. For a period of 8 weeks, participants aged 16 or older with at least mild eating disorder symptoms were randomized to four conditions: (1) Featback, (2) chat or e-mail support from an expert patient, (3) Featback with expert-patient support, and (4) a waitlist. A mixed-effects partitioning method was used to see if age, educational level, BMI, motivation to change, treatment history, duration of eating disorder, number of binge eating episodes in the past month, eating disorder pathology, self-efficacy, anxiety and depression, social support, or self-esteem predicted or moderated intervention outcomes in terms of eating disorder symptoms (primary outcome), and symptoms of anxiety and depression (secondary outcome).ResultsHigher baseline social support predicted less eating disorder symptoms 8 weeks later, regardless of condition. No variables emerged as moderator for eating disorder symptoms. Participants in the three active conditions who had not received previous eating disorder treatment, experienced larger reductions in anxiety and depression symptoms.DiscussionThe investigated online low-threshold interventions were especially beneficial for treatment-naïve individuals, but only in terms of secondary outcomes, making them well-suited for early intervention. The study results also highlight the importance of a supportive environment for individuals with eating disorder symptoms.Public SignificanceTo optimize treatment recommendations it is important to investigate what works for whom. For an internet-based intervention for eating disorders developed in the Netherlands, individuals who had never received eating disorder treatment seemed to benefit more from the intervention than those who had received eating disorder treatment, because they experienced larger reductions in symptoms of depression and anxiety. Stronger feelings of social support were related to less eating disorder symptoms in the future. Show less
Melisse, B.; Blankers, M.; Berg, E. van den; Jonge, M. de; Lommerse, N.; Furth, E. van; ... ; Beurs, E. de 2023
IntroductionThe aim is to perform an economic evaluation alongside a randomized controlled trial comparing guided self-help cognitive behavioral therapy-enhanced (CBT-E) for binge-eating disorder ... Show moreIntroductionThe aim is to perform an economic evaluation alongside a randomized controlled trial comparing guided self-help cognitive behavioral therapy-enhanced (CBT-E) for binge-eating disorder (BED) to a waiting list control condition. MethodsBED patients (N = 212) were randomly assigned to guided self-help CBT-E or the 3-month waiting list. Measurements took place at baseline and the end-of-treatment. The cost-effectiveness analysis was performed using the number of binge-eating episodes during the last 28 days as an outcome indicator according to the eating disorder examination. A cost-utility analysis was performed using the EuroQol-5D. ResultsThe difference in societal costs over the 3 months of the intervention between both conditions was euro679 (confidence interval [CI] 50-1330). The incremental costs associated with one incremental binge eating episode prevented in the guided self-help condition was approximately euro18 (CI 1-41). From a societal perspective there was a 96% likelihood that guided self-help CBT-E led to a greater number of binge-eating episodes prevented, but at higher costs. Each additional quality-adjusted life year (QALY) gained was associated with incremental costs of euro34,000 (CI 2494-154,530). With a 95% likelihood guided self-help CBT-E led to greater QALY gain at higher costs compared to waiting for treatment. Based on the National Institute for Health and Clinical Excellence willingness-to-pay threshold of euro35,000 per QALY, guided self-help CBT-E can be considered cost-effective with a likelihood of 95% from a societal perspective. DiscussionGuided self-help CBT-E is likely a cost-effective treatment for BED in the short-term (3-month course of treatment). Comparison to treatment-as-usual is recommended for future research, as it enables an economic evaluation with a longer time horizon. Public SignificanceOffering treatment remotely has several benefits for patients suffering from binge-eating disorders. Guided self-help CBT-E is an efficacious and likely cost-effective treatment, reducing binge eating and improving quality-of-life, albeit at higher societal costs. Show less
Melisse, B.; Berg, E. van den; Jonge, M. de; Blankers, M.; Furth, E. van; Dekker, J.; Beurs, E. de 2023
Background: Owing to the gap between treatment supply and demand, there are long waiting periods for patients with binge eating disorder, and there is an urgent need to increase their access to... Show moreBackground: Owing to the gap between treatment supply and demand, there are long waiting periods for patients with binge eating disorder, and there is an urgent need to increase their access to specialized treatment. Guided self-help cognitive behavioral therapy-enhanced (CBT-E) may have great advantages for patients if its efficacy can be established.Objective: The aim of this study was to examine the efficacy of guided self-help CBT-E compared with that of a delayed-treatment control condition.Methods: A single-blind 2-arm randomized controlled trial was designed to evaluate guided self-help CBT-E according to an intention-to-treat analysis. A total of 180 patients were randomly assigned to guided self-help CBT-E (n=90, 50%) or the delayed-treatment control condition (n=90, 50%) for which guided self-help CBT-E was provided after the initial 12-week delay. The primary outcome was reduction in binges. The secondary outcome was full recovery at the end of treatment, as measured using the Eating Disorder Examination during the last 4 weeks of treatment. A linear mixed model analysis was performed to compare treatment outcomes at the end of treatment. A second linear mixed model analysis was performed to measure between and within-group effects for up to 24 weeks of follow-up. The Eating Disorder Examination-Questionnaire and clinical impairment assessment were conducted before and after treatment and during follow-up. In addition, dropout rates were assessed in both conditions.Results: During the last 4 weeks of treatment, objective binges reduced from an average of 19 (SD 16) to 3 (SD 5) binges, and 40% (36/90) showed full recovery in the guided self-help CBT-E group. Between-group effect size (Cohen d) was 1.0 for objective binges. At follow-up, after both groups received treatment, there was no longer a difference between the groups. Of the 180 participants, 142 (78.9%) completed treatment. The overall treatment dropout appeared to be associated with gender, level of education, and number of objective binges at baseline but not with treatment condition.Conclusions: This is the first study to investigate the efficacy of guided self-help CBT-E. Guided self-help CBT-E appeared to be an efficacious treatment. This study's findings underscore the international guidelines recommending this type of treatment for binge eating disorder. Show less
Objectives: The benefit-risk ratio of many interventions remains unclear in older adults with dementia. Efforts for more representative trial inclusion are made; however, recruiting and... Show moreObjectives: The benefit-risk ratio of many interventions remains unclear in older adults with dementia. Efforts for more representative trial inclusion are made; however, recruiting and particularly gaining informed consent remains complex. For research participation, dementia compels the designation of a legal guardian (LG) to give proxy consent. To advance future trial development, we aimed to provide more insights into the factors that affect the proxy decision-making process in dementia research. Design: A qualitative analysis of semi-structured interviews about proxy decision-making on participation in dementia research. Setting and Participants: LGs of nursing home residents that gave (n = 19) and refrained from giving (n = 18) proxy consent for a clinical trial (the Danton study) in the Netherlands. Methods: Verbatim transcripts were thematically analyzed by using a preliminary deductive framework with room for induction of additional emerging themes, being an overall abductive approach. Based on that theme list, related factors of the decision-making process were grouped into overarching levels and merged into a step-by-step process. Results: When discussing proxy decision-making on the participation of an older adult with dementia in a clinical trial, LGs described interconnected factors on the level of the study and patient. Past experiences and attitudes of the LG influenced the weighing of these study- and patient-related factors, leading to a preliminary decision. Other proxies and treating health care professionals (HCPs) were named as important other stakeholders of the decision-making process. Conclusions and Implications: When giving proxy consent for research participation, LGs weigh study- and patient-related factors, leading to an initial benefit-risk evaluation. This weighing process is influenced by LG-related factors and can be modulated by other proxies or treating HCPs, leading to a definitive decision. Although insights into these underlying mechanisms could facilitate the proxy decision-making process for both LGs and researchers, treating HCPs could act as an independent party. (c) 2023 The Authors. Published by Elsevier Inc. on behalf of AMDA - The Society for Post-Acute and Long-Term Care Medicine. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Meertens, M.; Muntinghe-Wagenaar, M.B.; Sikkema, B.J.; Lopez-Yurda, M.; Retél, V.P.; Paats, M.S.; ... ; Wekken, A.J. van der 2023
Background: Alectinib is first-line therapy in patients with stage IV non-small cell lung carcinoma (NSCLC) and an anaplastic lymphoma kinase (ALK) fusion. A shorter median progression-free... Show moreBackground: Alectinib is first-line therapy in patients with stage IV non-small cell lung carcinoma (NSCLC) and an anaplastic lymphoma kinase (ALK) fusion. A shorter median progression-free survival (mPFS) was observed when alectinib minimum plasma concentrations during steady state (C-min,C-SS) were below 435 ng/mL. This may suggest that patients should have an alectinib C-min,C-SS=435 ng/mL for a more favorable outcome. This potential target could be attained by using therapeutic drug monitoring (TDM), i.e. adjusting the dose based on measured plasma trough concentrations. Hypothetically, this will increase mPFS, but this has not yet been evaluated in a randomized controlled trial (RCT). Therefore, the ADAPT ALEC trial is designed, with the primary objective to prolong mPFS in NSCLC patients treated with alectinib by using TDM.Methods: ADAPT ALEC is a multicenter, phase IV RCT, in which patients aged = 18 years with advanced ALK positive (+) NSCLC eligible for alectinib in daily care are enrolled. Participants will be randomized (1:1 ratio) into intervention arm A (TDM) or B (control), stratified by brain metastases and prior ALK treatments. Starting dose in both arms is the approved flat fixed dose of alectinib 600 mg taken twice daily with food. In case of alectinib C-min,C-SS < 435 ng/mL, arm A will receive increased doses of alectinib till C-min,C-SS = 435 ng/mL when considered tolerable. The primary outcome is mPFS, where progressive disease is defined according to RECIST v1.1 or all-cause death and assessed by CT-scans and MRI brain. Secondary endpoints are feasibility and tolerability of TDM, patient and physician adherence, overall response rate, median overall survival, intracranial PFS, quality of life, toxicity, alectinib-M4 concentrations and cost-effectiveness of TDM. Exploratory endpoints are circulating tumor DNA and body composition.Discussion: The ADAPT ALEC will show whether treatment outcomes of patients with advanced ALK+ NSCLC improve when using TDM-guided dosing of alectinib instead of fixed dosing. The results will provide high quality evidence for deciding whether TDM should be implemented as standard of care and this will have important consequences for the prescribing of alectinib. Show less
Cardol, C.K.; Middendorp, H. van; Dusseldorp, E.; Boog, P.J.M. van der; Hilbrands, L.B.; Navis, G.; ... ; E GOAL Study Grp 2023
Objective: Psychological distress is common among patients with chronic kidney disease and can interfere with disease self-management. We assessed the effectiveness of the personalized E-GOAL... Show moreObjective: Psychological distress is common among patients with chronic kidney disease and can interfere with disease self-management. We assessed the effectiveness of the personalized E-GOAL electronic health care pathway with screening and cognitive-behavioral therapy including self-management support, aimed to treat psychological distress and facilitate self-management among people with chronic kidney disease not on dialysis (N = 121). Methods: Primary outcome of the open two-arm parallel randomized controlled trial in four Dutch hospitals was psychological distress at posttest directly after the intervention and at 3-month follow-up. Secondary outcomes were physical and mental health-related quality of life, self-efficacy, chronic disease self-management, and personalized outcomes, that is, perceived progress compared with the previous time point on functioning (e.g., mood or social functioning) and self-management (e.g., dietary or medication adherence) outcomes that were prioritized by each individual. Results: Linear mixed-effects analyses showed no significant time-by-group interaction effects for psychological distress, health-related quality of life, self-efficacy, and chronic condition self-management, whereas analyses of covariance showed significantly more perceived progress in the intervention group at posttest on personally prioritized areas of functioning (b = 0.46, 95% confidence interval = 0.07-0.85) and self-management (b = 0.55, 95% confidence interval = 0.16-0.95), with Cohen d values of 0.46 and 0.54 (medium effects), respectively. Effects on personalized outcomes were maintained at follow-up. Conclusions: Compared with regular care only, the electronic health intervention did not reduce psychological distress, whereas personalized outcomes did improve significantly after intervention. Future studies could consider personalized outcomes that reflect individually relevant areas and treatment goals, matching person-tailored treatments. Show less
Background: The economic costs of mental disorders for society are huge. Internet-based interventions are often coined as cost-effective alternatives to usual care, but the evidence is mixed... Show moreBackground: The economic costs of mental disorders for society are huge. Internet-based interventions are often coined as cost-effective alternatives to usual care, but the evidence is mixed.Objective: The aim was to review the literature on the cost-effectiveness of internet interventions for mental disorders compared with usual care and to provide an estimate of the monetary benefits of such interventions compared with usual care.Methods: A systematic review and meta-analysis of randomized controlled trials was conducted, which included participants with symptoms of mental disorders; investigated a telephone- or internet-based intervention; included a control condition in the form of treatment as usual, psychological placebo, waiting list control, or bibliotherapy; reported outcomes on both quality of life and costs; and included articles published in English. Electronic databases such as PubMed (including MEDLINE), Embase, Emcare, PsycINFO, Web of Science, and the Cochrane Library were used. Data on risk of bias, quality of the economic evaluation, quality-adjusted life years, and costs were extracted from the included studies, and the incremental net benefit was calculated and pooled.Results: The search yielded 6226 abstracts, and 37 studies with 14,946 participants were included. The quality of economic evaluations of the included studies was rated as moderate, and the risk of bias was high. A random-effects approach was maintained. Analyses suggested internet interventions were slightly more effective than usual care in terms of quality-adjusted life years gain (Hedges g=0.052, 95% CI 0.010-0.094; P=.02) and equally expensive (Hedges g=0.002, 95% CI −0.080 to 0.84; P=.96). The pooled incremental net benefit was US $255 (95% CI US $91 to US $419; P=.002), favoring internet interventions over usual care. The perspective of the economic evaluation and targeted mental disorder moderated the results.Conclusions: The findings indicate that the cost-effectiveness of internet interventions for mental disorders compared with a care-as-usual approach is likely, but generalizability to new studies is poor given the substantial heterogeneity. This is the first study in the field of mental health to pool cost-effectiveness outcomes in an aggregate data meta-analysis. Show less
Sitsen, E.; Khalili-Mahani, N.; Rover, M. de; Dahan, A.; Niesters, M. 2022
Background: Spinal anesthesia causes short-term deafferentation and alters the crosstalk among brain regions involved in pain perception and pain modulation. In the current study, we examined the... Show moreBackground: Spinal anesthesia causes short-term deafferentation and alters the crosstalk among brain regions involved in pain perception and pain modulation. In the current study, we examined the effect of spinal anesthesia on pain response to noxious thermal stimuli in non-deafferented skin areas using a functional magnetic resonance imaging (fMRI) paradigm. Methods: Twenty-two healthy subjects participated in the study. We performed a task-based fMRI study using a randomized crossover design. Subjects were scanned under two conditions (spinal anesthesia or control) at two-time points: before and after spinal anesthesia. Spinal anesthesia resulted in sensory loss up to dermatome Th6. Calibrated heat-pain stimuli were administered to the right forearm (C8-Th1) using a box-car design (blocks of 10s on/25s off) during MRI scanning. Pain perception was measured using a visual analogue scale (1–100) at the beginning and the end of each session. Generalized estimating equations were used to examine the effect of intervention by time by order on pain scores. Similarly, higher level effects were tested with appropriate general linear models (accounting for within-subject variations in session and time) to examine: (1) Differences in BOLD response to pain stimulus under spinal anesthesia versus control; and (2) Effects of spinal anesthesia on pain-related modulation of the cerebral activation. Results: Complete fMRI data was available for eighteen participants. Spinal anesthesia was associated with moderate pain score increase. Significant differences in brain response to noxious thermal stimuli were present in comparison of spinal versus control condition (post—pre). Spinal condition was associated with higher BOLD signal in the bilateral inferior parietal lobule and lower BOLD signal in bilateral postcentral and precentral gyrus. Within the angular regions, we observed a positive correlation between pain scores and BOLD signal. These observations were independent from order effect (whether the spinal anesthesia was administered in the first or the second visit). However, we did observe order effect on brain regions including medial prefrontal regions, possibly related to anticipation of the experience of spinal anesthesia. Conclusions: The loss of sensory and motor activity caused by spinal anesthesia has a significant impact on brain regions involved in the sensorimotor and cognitive processing of noxious heat pain stimuli. Our results indicate that the anticipation or experience of a strong somatosensory response to the spinal intervention might confound and contribute to increased sensitivity to cognitive pain processing. Future studies must account for individual differences in subjective experience of pain sensation within the experimental context Show less
STUDY QUESTION: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in... Show moreSTUDY QUESTION: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in terms of live births? SUMMARY ANSWER: In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of EM is inferior compared to IUI-OS in terms of live births. WHAT IS KNOWN ALREADY: Couples with unexplained subfertility and a poor prognosis are often treated with IUI-OS. In couples with unexplained subfertility and a relatively good prognosis for natural conception (>30% in 12 months), IUI-OS does not increase the live birth rate as compared to 6 months of EM. However, in couples with a poor prognosis for natural conception (<30% in 12 months), the effectiveness of IUI-OS is uncertain. STUDY DESIGN, SIZE, DURATION: We performed a non-inferiority multicentre randomized controlled trial within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We intended to include 1091 couples within 3 years. The couples were allocated in a 1:1 ratio to 6 months EM or 6 months IUI-OS with either clomiphene citrate or gonadotrophins. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied heterosexual couples with unexplained subfertility and a poor prognosis for natural conception (<30% in 12 months). The primary outcome was ongoing pregnancy leading to a live birth. Non-inferiority would be shown if the lower limit of the one-sided 90% risk difference (RD) CI was less than minus 7% compared to an expected live birth rate of 30% following IUI-OS. We calculated RD, relative risks (RRs) with 90% CI and a corresponding hazard rate for live birth over time based on intention-to-treat and per-protocol (PP) analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Between October 2016 and September 2020, we allocated 92 couples to EM and 86 to IUI-OS. The trial was halted pre-maturely owing to slow inclusion. Mean female age was 34 years, median duration of subfertility was 21 months. Couples allocated to EM had a lower live birth rate than couples allocated to IUI-OS (12/92 (13%) in the EM group versus 28/86 (33%) in the IUI-OS group; RR 0.40 90% CI 0.24 to 0.67). This corresponds to an absolute RD of minus 20%; 90% CI: -30% to -9%. The hazard ratio for live birth over time was 0.36 (95% CI 0.18 to 0.70). In the PP analysis, live births rates were 8 of 70 women (11%) in the EM group versus 26 of 73 women (36%) in the IUI-OS group (RR 0.32, 90% CI 0.18 to 0.59; RD -24%, 90% CI -36% to -13%) in line with inferiority of EM. LIMITATIONS, REASONS FOR CAUTION: Our trial did not reach the planned sample size, therefore the results are limited by the number of participants. WIDER IMPLICATIONS OF THE FINDINGS: This study confirms the results of a previous trial that in couples with unexplained subfertility and a poor prognosis for natural conception, EM is inferior to IUI-OS. Show less
Aim: We assessed whether total sleep deprivation (TSD) in combination with pain tests yields a reliable method to assess altered pain thresholds, which subsequently may be used to investigate ... Show moreAim: We assessed whether total sleep deprivation (TSD) in combination with pain tests yields a reliable method to assess altered pain thresholds, which subsequently may be used to investigate (novel) analgesics in healthy subjects. Methods: This was a two-part randomized crossover study in 24 healthy men and 24 women. Subjects were randomized 1:1 to first complete a day of nonsleep-deprived nociceptive threshold testing, followed directly by a TSD night and morning of sleep-deprived testing, or first complete the TSD night and morning sleep-deprived testing, returning 7 days later for a day of nonsleep-deprived testing. A validated pain test battery (heat, pressure, electrical burst and stair, cold pressor pain test and conditioned pain modulation [CPM] paradigm) and sleep questionnaires were performed. Results: Subjects were significantly sleepier after TSD as measured using sleepiness questionnaires. Cold pressor pain tolerance (PTT, estimate of difference [ED] -10.8%, 95% CI -17.5 to -3.6%), CPM PTT (ED -0.69 mA, 95% CI -1.36 to -0.03 mA), pressure PTT (ED -11.2%, 95% CI -17.5% to -4.3%) and heat pain detection thresholds (ED -0.74 degrees C, 95% CI -1.34 to -0.14 degrees C) were significantly decreased after TSD compared to the baseline morning assessment in the combined analysis (men + women). Heat hyperalgesia was primarily driven by an effect of TSD in men, whereas cold and pressure hyperalgesia was primarily driven by the effects of TSD observed in women. Conclusions: TSD induced sex-dependent hyperalgesia on cold, heat and pressure pain, and CPM response. These results suggest that the TSD model may be suitable to evaluate (novel) analgesics in early-phase drug studies. Show less
Rohrbach, P.J.; Dingemans, A.E.; Spinhoven, P.; Ginkel, J.R. van; Fokkema, M.; Wilderjans, T.F.; ... ; Furth, E.F. van 2022
Objective: Many individuals with an eating disorder do not receive appropriate care. Low-threshold interventions could help bridge this treatment gap. The study aim was to evaluate the... Show moreObjective: Many individuals with an eating disorder do not receive appropriate care. Low-threshold interventions could help bridge this treatment gap. The study aim was to evaluate the effectiveness of Featback, a fully automated online self-help intervention, online expert-patient support and their combination. Method: A randomized controlled trial with a 12-month follow-up period was conducted. Participants aged 16 or older with at least mild eating disorder symptoms were randomized to four conditions: (1) Featback, a fully automated online self-help intervention, (2) chat or email support from a recovered expert patient, (3) Featback with expert-patient support and (4) a waiting list control condition. The intervention period was 8 weeks and there was a total of six online assessments. The main outcome constituted reduction of eating disorder symptoms over time. Results: Three hundred fifty five participants, of whom 43% had never received eating disorder treatment, were randomized. The three active interventions were superior to a waitlist in reducing eating disorder symptoms (d = -0.38), with no significant difference in effectiveness between the three interventions. Participants in conditions with expert-patient support were more satisfied with the intervention. Discussion: Internet-based self-help, expert-patient support and their combination were effective in reducing eating disorder symptoms compared to a waiting list control condition. Guidance improved satisfaction with the internet intervention but not its effectiveness. Low-threshold interventions such as Featback and expert-patient support can reduce eating disorder symptoms and reach the large group of underserved individuals, complementing existing forms of eating disorder treatment. Public significance statement: Individuals with eating-related problems who received (1) a fully automated internet-based intervention, (2) chat and e-mail support by a recovered individual or (3) their combination, experienced stronger reductions in eating disorder symptoms than those who received (4) usual care. Such brief and easy-access interventions play an important role in reaching individuals who are currently not reached by other forms of treatment. Show less
Objective The primary aim was assessing the cost-effectiveness of an internet-based self-help program, expert-patient support, and the combination of both compared to a care-as-usual condition.... Show moreObjective The primary aim was assessing the cost-effectiveness of an internet-based self-help program, expert-patient support, and the combination of both compared to a care-as-usual condition. Method :An economic evaluation from a societal perspective was conducted alongside a randomized controlled trial. Participants aged 16 or older with at least mild eating disorder symptoms were randomly assigned to four conditions: (1) Featback, an online unguided self-help program, (2) chat or e-mail support from a recovered expert patient, (3) Featback with expert-patient support, and (4) care-as-usual. After a baseline assessment and intervention period of 8 weeks, five online assessments were conducted over 12 months of follow-up. The main result constituted cost-utility acceptability curves with quality-of-life adjusted life years (QALYs) and societal costs over the entire study duration. Results: No significant differences between the conditions were found regarding QALYs, health care costs and societal costs. Nonsignificant differences in QALYs were in favor of the Featback conditions and the lowest societal costs per participant were observed in the Featback only condition (euro16,741) while the highest costs were seen in the care-as-usual condition (euro28,479). The Featback only condition had the highest probability of being efficient compared to the alternatives for all acceptable willingness-to-pay values. Discussion: Featback, an internet-based unguided self-help intervention, was likely to be efficient compared to Featback with guidance from an expert patient, guidance alone and a care-as-usual condition. Results suggest that scalable interventions such as Featback may reduce health care costs and help individuals with eating disorders that are currently not reached by other forms of treatment. Public significance statement: Internet-based interventions for eating disorders might reach individuals in society who currently do not receive appropriate treatment at low costs. Featback, an online automated self-help program for eating disorders, was found to improve quality of life slightly while reducing costs for society, compared to a do-nothing approach. Consequently, implementing internet-based interventions such as Featback likely benefits both individuals suffering from an eating disorder and society as a whole. Show less
Study Design: Randomized controlled trial. Objective: Percutaneous transforaminal endoscopic discectomy (PTED) was introduced as a less invasive procedure to treat sciatica. Even though the PTED... Show moreStudy Design: Randomized controlled trial. Objective: Percutaneous transforaminal endoscopic discectomy (PTED) was introduced as a less invasive procedure to treat sciatica. Even though the PTED has a small scar size, it is unknown if PTED also leads to better scar-related patient-reported outcomes. Therefore, we aimed to compare scar-related outcomes between patients undergoing PTED vs open microdiscectomy. Methods: Patients with at least 6 weeks of radiating leg pain were randomized in a 1:1 ratio to PTED or open microdiscectomy. Scar-related patient-reported outcomes were measured using the Body Image Score (BIS), Cosmesis Scale (CS) and a 0-10 numeric rating scale (NRS) on scar esthetic. Results: Of the 530 included patients, 286 patients underwent PTED and 244 underwent open microdiscectomy as allocated. At 12 months of follow-up, 95% of the patients had data available. At 12 months, the BIS was 6.2 +/- 1.7 in the PTED-group and 6.6 +/- 1.9 in the open microdiscectomy group (between-group difference .4, 95% CI .2 to .7). CS was 21.3 +/- 3.0 in the PTED-group and 18.6 +/- 3.4 in the open microdiscectomy group (between-group difference -2.7, 95% CI -3.1 to -2.3). Average NRS for scar esthetic was 9.2 +/- 1.3 and 7.8 +/- 1.6 in the PTED and open microdiscectomy groups, respectively (between-group difference -1.4, 95% CI -1.6 to -1.2). Conclusions: PTED leads to a higher self-rated scar esthetic as compared to open microdiscectomy, while self-reported body image seems to be comparable between both groups. Therefore, from an esthetic point, PTED seems to be the preferred technique to treat sciatica. Show less
Objective To assess the costs and cost-effectiveness of percutaneous transforaminal endoscopic discectomy (PTED) compared with open microdiscectomy among patients with sciatica.Methods This... Show moreObjective To assess the costs and cost-effectiveness of percutaneous transforaminal endoscopic discectomy (PTED) compared with open microdiscectomy among patients with sciatica.Methods This economic evaluation was conducted alongside a 12-month multicentre randomised controlled trial with a non-inferiority design, in which patients were randomised to PTED or open microdiscectomy. Patients were aged from 18 to 70 years and had at least 6 weeks of radiating leg pain caused by lumbar disc herniation. Effect measures included leg pain and quality-adjusted life years (QALYs), as derived using the EQ-5D-5L. Costs were measured from a societal perspective. Missing data were multiply imputed, bootstrapping was used to estimate statistical uncertainty, and various sensitivity analyses were conducted to determine the robustness.Results Of the 613 patients enrolled, 304 were randomised to PTED and 309 to open microdiscectomy. Statistically significant differences in leg pain and QALYs were found in favour of PTED at 12 months follow-up (leg pain: 6.9; 95% CI 1.3 to 12.6; QALYs: 0.040; 95% CI 0.007 to 0.074). Surgery costs were higher for PTED than for open microdiscectomy (ie, euro4500/patient vs euro4095/patient). All other disaggregate costs as well as total societal costs were lower for PTED than for open microdiscectomy. Cost-effectiveness acceptability curves indicated that the probability of PTED being less costly and more effective (ie, dominant) compared with open microdiscectomy was 99.4% for leg pain and 99.2% for QALYs.Conclusions Our results suggest that PTED is more cost-effective from the societal perspective compared with open microdiscectomy for patients with sciatica. Show less
Ebbens, M.M.; Gombert-Handoko, K.B.; Wesselink, E.J.; Bemt, P.M.L.A. van den 2021
Background: Medication reconciliation has become standard care to prevent medication transfer errors. However, this process is time-consuming but could be more efficient when patients are engaged... Show moreBackground: Medication reconciliation has become standard care to prevent medication transfer errors. However, this process is time-consuming but could be more efficient when patients are engaged in medication reconciliation via a patient portal. Objectives: To explore whether medication reconciliation by the patient via a patient portal is noninferior to medication reconciliation by a pharmacy technician. Design (including intervention): Open randomized controlled noninferiority trial. Patients were randomized between medication reconciliation via a patient portal (intervention) or medication reconciliation by a pharmacy technician at the preoperative screening (usual care). Setting and Participants: Patients scheduled for elective surgery using at least 1 chronic medication were included. Measures: The primary endpoint was the number of medication discrepancies compared to the electronic nationwide medication record system (NMRS). For the secondary endpoint, time investment of the pharmacy technician for the medication reconciliation interview and patient satisfaction were studied. Noninferiority was analyzed with an independent t test, and the margin was set at 20%. Results: A total of 499 patients were included. The patient portal group contained 241 patients; the usual care group contained 258 patients. The number of medication discrepancies was 2.6 +/- 2.5 in the patient portal group and 2.8 +/- 2.7 in the usual care group. This was not statistically different and within the predefined noninferiority margin. Patients were satisfied with the use of the patient portal tool. Also, the use of the portal can save on average 6.8 minutes per patient compared with usual care. Conclusions and Implications: Medication reconciliation using a patient portal is noninferior to medication reconciliation by a pharmacy technician with respect to medication discrepancies, and saves time in the medication reconciliation process. Future studies should focus on identifying patient characteristics for successful implementation of patient portal medication reconciliation. (c) 2021 The Authors. Published by Elsevier Inc. on behalf of AMDA -The Society for Post-Acute and Long-Term Care Medicine. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Wissen, M.A.T. van; Teuwen, M.M.H.; Ende, C.H.M. van den; Vlieland, T.P.M.V.; Broeder, A.A. den; Hout, W.B. van den; ... ; Weely, S.F.E. van 2021
Objectives Research on effectiveness and cost-effectiveness of longstanding exercise therapy in patients with axial SpondyloArthritis (axSpA) or Rheumatoid Arthritis (RA) is scarce, and mainly... Show moreObjectives Research on effectiveness and cost-effectiveness of longstanding exercise therapy in patients with axial SpondyloArthritis (axSpA) or Rheumatoid Arthritis (RA) is scarce, and mainly concerned patients with a relatively favorable health status. We aim to evaluate the effectiveness and cost-effectiveness of longstanding exercise therapy compared to usual care in the subgroup of patients with axSpA or RA and severe limitations in functioning. Methods In two separate, parallel randomized controlled trials the effectiveness and cost-effectiveness of longstanding, active exercise therapy (52 weeks) compared with usual care (1:1) will be evaluated. The longstanding, active exercise therapy will focus on improving individual limitations in daily activities and participation and will be given by a trained physical therapist in the vicinity of the participant. For each diagnosis, 215 patients with severe limitations in activities and participation will be included. Assessments are performed at baseline, 12, 26, and 52 weeks. The primary outcome measure of effectiveness is the individual level of functioning (activities and participation), as measured with the Patient-Specific Complaints instrument at 52 weeks. For cost-effectiveness analyses, the EuroQol (EQ-5D-5L) and questionnaires on healthcare use and productivity will be administered. The economic evaluation will be a cost-utility analysis from a societal perspective. After 52 weeks, the patients in the usual care group are offered longstanding, active exercise therapy as well. Follow-up assessments are done at 104, 156, and 208 weeks. Conclusion The results of these studies will provide insights in the effectiveness and cost-effectiveness of longstanding exercise therapy in the subgroup of axSpA and RA patients with severe functional limitations. Show less
Starreveld, D.E.J.; Daniels, L.A.; Kieffer, J.M.; Valdimarsdottir, H.B.; Geus, J. de; Lanfermeijer, M.; ... ; Bleiker, E.M.A. 2021
Simple SummaryCancer-related fatigue (CRF) is one of the most frequently reported symptoms with prevalence rates of 25 to 60 percent in (non-)Hodgkin lymphoma survivors. Several (pilot) studies... Show moreSimple SummaryCancer-related fatigue (CRF) is one of the most frequently reported symptoms with prevalence rates of 25 to 60 percent in (non-)Hodgkin lymphoma survivors. Several (pilot) studies showed promising effects of light therapy to reduce CRF. The aim of the current study is to evaluate the short- and long-term efficacy of light therapy on CRF and associated symptoms in chronically fatigued (non-)Hodgkin lymphoma survivors. Eighty-three survivors were exposed to bright white light (intervention) and another 83 survivors were exposed to dim white light (comparison). Results showed that all participants, irrespective of light condition, reported reduced levels of fatigue after the completion of light therapy. Similar results were found for depression, sleep quality, and some aspects of quality of life. No effect was found on circadian rhythms or objectively assessed sleep. Therefore, it is important to further investigate which aspects of intervention are associated with the improvements observed after light therapy.Purpose: To evaluate the short- and long-term effects of light therapy on fatigue (primary outcome) and sleep quality, depression, anxiety, quality of life, and circadian rhythms (secondary outcomes) in survivors of (non-)Hodgkin lymphoma presenting with chronic cancer-related fatigue. Methods: We randomly assigned 166 survivors (mean survival 13 years) to a bright white light intervention (BWL) or dim white light comparison (DWL) group. Measurements were completed at baseline (T0), post-intervention (T1), at three (T2), and nine (T3) months follow-up. A mixed-effect modeling approach was used to compare linear and non-linear effects of time between groups. Results: There were no significant differences between BWL and DWL in the reduction in fatigue over time. Both BWL and DWL significantly (p < 0.001) improved fatigue levels during the intervention followed by a slight reduction in this effect during follow-up (EST0-T1 = -0.71; EST1-T3 = 0.15). Similar results were found for depression, sleep quality, and some aspects of quality of life. Light therapy had no effect on circadian rhythms. Conclusions: BWL was not superior in reducing fatigue compared to DWL in HL and DLBCL survivors. Remarkably, the total sample showed clinically relevant and persistent improvements on fatigue not commonly seen in longitudinal observational studies in these survivors. Show less
